Trial reportArthritis research & therapy2019
Safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06650833, a selective interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor, in single and multiple ascending dose randomized phase 1 studies in healthy subjects.
Trial report in Arthritis research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1, Randomized, Double Blind, Sponsor Open, Placebo Substitution, Crossover, Single Dose Escalation Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Pf 06650833 Delivered In Multiple Formulations In Healthy Subjects Under Fasted And Fed Conditions
A Phase 1, Randomized, Double Blind, Sponsor Open, Placebo Controlled, Sequential Group, Multiple Ascending Dose Escalation Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Orally Administered Pf 06650833 In Healthy Subjects
Who cites it
33 citing papers in PubMed, 61 citations in OpenAlex.
- Pharmacokinetics and Pharmacodynamics of KT-474, a Novel Selective Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) Degrader, in Healthy Adults.Clinical and translational science · 2025Trial
- IRAK4 degrader in hidradenitis suppurativa and atopic dermatitis: a phase 1 trial.Nature medicine · 2023Trial
- The Interleukin-1 Receptor-Associated Kinase 4 Inhibitor PF-06650833 Blocks Inflammation in Preclinical Models of Rheumatic Disease and in Humans Enrolled in a Randomized Clinical Trial.Arthritis & rheumatology (Hoboken, N.J.) · 2021Trial
- Innate immunity: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Efficacy and Safety of Zabedosertib, an Interleukin-1 Receptor-Associated Kinase 4 Inhibitor, in Patients with Moderate-to-Severe Atopic Dermatitis: A Phase II Randomized Study.Dermatology and therapy · 2025Article
- Dendritic cell heterogeneity and its role in connective tissue diseases.Inflammation and regeneration · 2025Review
- Involvement of nucleic acid-sensing toll-like receptors in human diseases and their controlling mechanisms.Journal of biomedical science · 2025Review
- Blood-Brain Barrier-Penetrating Nanocarriers Enable Microglial-Specific Drug Delivery in Hypothalamic Neuroinflammation.Advanced healthcare materials · 2025Article
- Zabedosertib, a novel interleukin-1 receptor-associated kinase-4 inhibitor, shows a favorable pharmacokinetic and safety profile across multiple phase 1 studies.Frontiers in pharmacology · 2025Article
- Blockade of IL-1 family cytokines in the treatment of rheumatoid arthritis.Frontiers in pharmacology · 2025Review
- CONSORT-DEFINE explanation and elaboration: recommendations for enhancing reporting quality and impact of early phase dose-finding clinical trials.EClinicalMedicine · 2025Article
- Emerging interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitors or degraders as therapeutic agents for autoimmune diseases and cancer.Acta pharmaceutica Sinica. B · 2024Review
- Exogenous interleukin-1 beta stimulation regulates equine tenocyte function and gene expression in three-dimensional culture which can be rescued by pharmacological inhibition of interleukin 1 receptor, but not nuclear factor kappa B, signaling.Molecular and cellular biochemistry · 2024Article
- In Retrospect: Root-Cause Analysis of Structure-Activity Relationships in IRAK4 Inhibitor Zimlovisertib (PF-06650833).ACS medicinal chemistry letters · 2024Article
- Targeting TLR Signaling Cascades in Systemic Lupus Erythematosus and Rheumatoid Arthritis: An Update.Biomedicines · 2024Article
- Targeted Nanocarriers for Systemic Delivery of IRAK4 Inhibitors to Inflamed Tissues.Small (Weinheim an der Bergstrasse, Germany) · 2024Article
- Metabolic changes in fibroblast-like synoviocytes in rheumatoid arthritis: state of the art review.Frontiers in immunology · 2024Review
- Toll-like receptor signalling via IRAK4 affects epithelial integrity and tightness through regulation of junctional tension.Development (Cambridge, England) · 2023Article
- PROTACs reach clinical development in inflammatory skin disease.Nature medicine · 2023Article
- Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus.Medicina (Kaunas, Lithuania) · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPF-06650833 is a potent, selective inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4). Two randomized, double-blind, sponsor-open phase 1 studies evaluated the safety, pharmacokinetics, and pharmacodynamics of single (SAD) and multiple ascending doses (MAD) of PF-06650833 immediate-release (IR) and modified-release (MR) oral formulations in healthy adult subjects.
methodsStudy 1 (NCT02224651) was a 96-day, placebo-substitution, SAD study of once-daily (QD) oral PF-06650833 IR 1 to 6000 mg and MR 30 to 300 mg in fasted and fed states. Study 2 (NCT02485769) was a 14-day, placebo-controlled, MAD study of PF-06650833 IR 25 to 750 mg twice daily, IR 1000 mg four times per day, IR 330 mg three times per day, and MR 300 mg QD.
resultsPF-06650833 was generally well tolerated, with no dose-limiting treatment-emergent adverse events (TEAEs) identified in either study. TEAEs were generally mild in severity, with headache, gastrointestinal disorders, and acne most commonly reported. No serious AEs or deaths were reported. A maximum tolerated dose was not established in either study. In the SAD study, food intake delayed absorption of IR 30 mg and increased total exposure by 33%. Delayed absorption was achieved with the MR formulation (T
conclusionsPF-06650833, the first IRAK4 inhibitor to enter clinical development, has a favorable safety and pharmacokinetic profile and has shown evidence of pharmacological effect. The data support continued evaluation in human clinical trials for the treatment of rheumatic and autoimmune diseases.
trial registrationClinicaltrials.gov, NCT02224651, registered 25 August 2014; NCT02485769, registered 30 June 2015.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.